Publications by authors named "Valérie Lauer"

7 Publications

  • Page 1 of 1

Heterozygous HTRA1 nonsense or frameshift mutations are pathogenic.

Brain 2021 Jul 16. Epub 2021 Jul 16.

AP-HP, Service de Génétique Moléculaire Neurovasculaire, Hôpital Saint-Louis, France.

Heterozygous missense HTRA1 mutations have been associated with an autosomal dominant cerebral small vessel disease whereas the pathogenicity of heterozygous HTRA1 stop codon variants is unclear. We performed a targeted high throughput sequencing of all known cerebral small vessel disease genes, including HTRA1, in 3,853 unrelated consecutive CSVD patients referred for molecular diagnosis. The frequency of heterozygous HTRA1 mutations leading to a premature stop codon in this patient cohort was compared with their frequency in large control databases. An analysis of HTRA1 messenger RNA was performed in several stop codon carrier patients. Clinical and neuroimaging features were characterized in all probands. Twenty unrelated patients carrying a heterozygous HTRA1 variant leading to a premature stop codon were identified. A highly significant difference was observed when comparing our patient cohort with control databases (gnomAD v3.1.1 (p = 3.12 x 10-17, OR = 21.9), TOPMed freeze 5 (p = 7.6 x 10-18, OR = 27.1) and 1000 Genomes (p = 1.5 x 10-5). Messenger RNA analysis performed in eight patients showed a degradation of the mutated allele strongly suggesting a haploinsufficiency. Clinical and neuroimaging features are similar to those previously reported in heterozygous missense mutation carriers, except for penetrance, which seems lower. Altogether, our findings strongly suggest that heterozygous HTRA1 stop codons are pathogenic through a haploinsufficiency mechanism. Future work will help to estimate their penetrance, an important information for genetic counseling.
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http://dx.doi.org/10.1093/brain/awab271DOI Listing
July 2021

Ischaemic strokes with reversible vasoconstriction and without thunderclap headache: a variant of the reversible cerebral vasoconstriction syndrome?

Cerebrovasc Dis 2015 24;39(1):31-8. Epub 2014 Dec 24.

Unité Neuro-Vasculaire, Service de Neurologie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.

Background: Reversible vasoconstriction (RV) may cause ischaemic stroke (IS) in the absence of any other defined stroke aetiology. The three objectives of our study were to evaluate the frequency of RV in a prospective series of young IS patients, to describe the detailed clinical-radiological features in the patients with RV and IS, and to compare these characteristics with those of reversible cerebral vasoconstriction syndrome (RCVS).

Methods: We identified between October 2005 and December 2010, 159 consecutive young patients (<45 years) hospitalized for an acute IS confirmed by cerebral magnetic resonance imaging. An extensive diagnostic work-up was performed including toxicological urinary screening for cannabis, cocaine and amphetamines, and the usual biological, cardiac and vascular investigations for an IS in the young. We specifically studied patients with IS and RV, which was defined as multifocal intracranial arterial stenoses confirmed by intracranial arterial imaging that resolved within 3-6 months.

Results: Out of 159 patients with IS, 21 (13%, 12 males, 9 females; mean age 32 years) had multifocal cerebral arterial stenoses that were fully reversible at 3-6 months, and no other cause for stroke. IS were located on posterior territory in 71% of cases, and vasoconstriction predominated on posterior cerebral and superior cerebellar arteries. Precipitating factors of IS and RV were the use of cannabis resin (n = 14), nasal decongestants (n = 2) and triptan (n = 1). Most cases (74%) had unusual severe headache, but none had thunderclap headache. None of 21 cases had reversible posterior leukoencephalopathy, cortical subarachnoid or intracerebral haemorrhage.

Conclusion: RV was the sole identified cause of IS in 13% of our cohort. These young patients with IS and RV may have a variant of RCVS, related to an increased susceptibility to vasoactive agents in some individuals. RV in our patients differs from the classical characteristics of RCVS by the absence of thunderclap headache, reversible brain oedema and subarachnoid or intracranial haemorrhage. Intracranial arteries should be looked for, by appropriate vascular imaging, in young patients with IS at the acute stage and during the follow-up period.
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http://dx.doi.org/10.1159/000369776DOI Listing
October 2015

High frequency of intracranial arterial stenosis and cannabis use in ischaemic stroke in the young.

Cerebrovasc Dis 2014 23;37(6):438-43. Epub 2014 Jul 23.

Unité Neuro-Vasculaire, Hôpitaux Universitaires de Strasbourg (HUS), Strasbourg, France.

Background: Leading aetiologies of ischaemic stroke in young adults are cervico-cerebral arterial dissections and cardio-embolism, but the causes remain undetermined in a considerable proportion of cases. In a few reports, intracranial arterial stenosis has been suggested to be a potential cause of ischaemic stroke in young adults. The aim of our work was to evaluate the frequency, characteristics and risk factors of intracranial arterial stenosis in a prospective series of young ischaemic stroke patients.

Methods: The study was based on a prospective consecutive hospital-based series of 159 patients aged 18-45 years who were admitted to our unit for an acute ischaemic stroke from October 2005 to December 2010. A structured questionnaire was used in order to assess common vascular risk factors such as hypertension, diabetes, hypercholesterolemia, use of tobacco, alcohol and illicit drugs, migraine, and, in women, oral contraceptive use. A systematic screening was performed, including the following: brain magnetic resonance imaging or, if not feasible, brain computed tomography scan, carotid and vertebral Duplex scanning and trans-cranial Doppler sonography, 3D time-of-flight magnetic resonance cerebral angiography or cerebral computed tomography angiography. Long-duration electrocardiography, trans-thoracic and trans-oesophageal echocardiography were performed and laboratory blood investigations were extensive. Urine samples were screened for cannabinoids, cocaine, amphetamine and methylene-dioxy-methamphetamine. When this initial work-up was inconclusive, trans-femoral intra-arterial selective digital subtraction angiography with reconstructed 3D images was performed.

Results: In this series, 49 patients (31%) had intracranial arterial stenosis. Other defined causes were found in 91 patients (57%), including cardio-embolism in 32 (20%), cervical dissection in 23 (14%), extracranial atherosclerosis in 7 (4%), haematological disorders in 7 (4%), small vessel disease in 1, and isolated patent foramen ovale in 21 (13%); in 19 patients (12%), ischaemic stroke was related to an undetermined aetiology. Comparing risk factors between patients with intracranial arterial stenosis and those with other definite causes showed that there were only two significant differences: a lower age and a higher frequency of vasoactive substances (especially cannabis) in patients with intracranial arterial stenosis. All intracranial arterial stenosis in patients who used vasoactive substances were located in several intracranial vessels.

Conclusions: Intracranial arterial stenosis may be an important mechanism of stroke in young patients and it should be systematically investigated using vascular imaging. Strong questioning about illicit drug consumption (including cannabis) or vasoactive medication use should also be performed. It should be emphasized for health prevention in young adults that cannabis use might be associated with critical consequences such as stroke.
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http://dx.doi.org/10.1159/000363618DOI Listing
June 2015

Cannabis-related stroke: myth or reality?

Stroke 2013 Feb 27;44(2):558-63. Epub 2012 Dec 27.

Unité Neuro-Vasculaire, Hôpitaux Universitaires de Strasbourg, 67085 Strasbourg Cedex, France.

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http://dx.doi.org/10.1161/STROKEAHA.112.671347DOI Listing
February 2013

[Indications for thrombolysis in ischemic stroke].

Presse Med 2012 May 23;41(5):504-13. Epub 2012 Feb 23.

Hôpital de Hautepierre, hôpitaux universitaires de Strasbourg, pôle tête et cou, unité neurovasculaire, 67098 Strasbourg cedex, France.

Cerebral MRI with angio-MR are more effective than CT scan for selecting patients with ischemic stroke for thrombolysis. The use of cerebral MRI has to be available 24h a day and everyday as a standardized emergency procedure. Off-label criteria for thrombolysis after acute ischemic stroke are too restritive and have to be revised. In acute ischemic stroke, imaging that shows the collateral circulation within the hypoperfusion area has to be used to estimate the potential of therapeutic revascularization. When there are contraindications for intravenous thrombolysis, the endovascular approach must be argued individually by neurologists and neurointerventionalists together.
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http://dx.doi.org/10.1016/j.lpm.2011.11.029DOI Listing
May 2012

Cannabis use, ischemic stroke, and multifocal intracranial vasoconstriction: a prospective study in 48 consecutive young patients.

Stroke 2011 Jun 21;42(6):1778-80. Epub 2011 Apr 21.

Unite´ Neuro-Vasculaire, Hôpitaux Universitaires de Strasbourg, France.

Background And Purpose: Our objective was to evaluate the relationship between cannabis use and ischemic stroke in a young adult population.

Methods: Forty-eight consecutive young patients admitted for acute ischemic stroke participated in the study. First-line screening was performed, including blood tests, cardiovascular investigations, and urine analysis for cannabinoids. If no etiology was found, 3D rotational angiography and cerebrospinal fluid analysis were performed. A control was planned through neurovascular imaging within 3 to 6 months.

Results: In this series, there was multifocal intracranial stenosis associated with cannabis use in 21% (n=10).

Conclusions: Multifocal angiopathy associated with cannabis consumption could be an important cause of ischemic stroke in young people.
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http://dx.doi.org/10.1161/STROKEAHA.110.610915DOI Listing
June 2011

Tacrolimus-associated posterior reversible encephalopathy syndrome after solid organ transplantation.

Eur Neurol 2010 12;64(3):169-77. Epub 2010 Aug 12.

The Second Affiliated Hospital , Chongqing Medical University, Chongqing, PR China.

Tacrolimus (TAC) is an immunosuppressant drug discovered in 1984 by Fujisawa Pharmaceutical Co., Ltd. This drug belongs to the group of calcineurin inhibitors, which has been proven highly effective in preventing acute rejection after transplantation of solid organs. However, neurotoxicity and nephrotoxicity are its major adverse effects. Posterior reversible encephalopathy syndrome (PRES) is the most severe and dramatic consequence of calcineurin inhibitor neurotoxicity. It was initially described by Hinchey et al. in 1996 [N Engl J Med 1996;334:494-450]. Patients typically present with altered mental status, headache, focal neurological deficits, visual disturbances, and seizures. Magnetic resonance imaging is the most sensitive imaging test to detect this. With the more deep-going studies done recently, we have learnt more about this entity. It was noted that this syndrome is frequently reversible, rarely limited to the posterior regions of the brain, and often located in gray matter and cortex as well as in white matter. Therefore, in this review, the focus is on the current understanding of clinical recognition, pathogenesis, neuroimaging and management of TAC-associated PRES after solid organ transplantation.
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http://dx.doi.org/10.1159/000319032DOI Listing
December 2010
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